We are still seeking information about the inter-relationship between a primary tumor and the tumor specific immune response to the host. In a series of investigations, regional lymph nodes (RLN's) of tumor bearing mice showed increased number of pyroninophilic cells, which decreased following tumor removal. The finding of a decrease is paradoxical in that tumor immunity persists. It does, however, coincide with a decrease in in vitro cytotoxicity by RLNC's suggesting that the pyroninophilic elements, vis-a-vis immunoblasts, may be more closely related to cytotoxicity than to tumor immunity per se. The latter may be more closely related to follicle formation of RLN's. In other investigations a. the cytotoxicity of cultured macrophages is highly tumor specific, b. cells from RLN's may affect stem cells for which cultured macrophages (CMA's) are derived, c. the cytotoxicity of CMA's is inhibited by serum from tumor bearing animals and the degree of inhibition increases with duration of tumor growth in the serum donor, and d. with progressive tumor growth, bone marrow cells result in CMA's with decreased cytotoxicity. A third study indicated that circulating granulocytes in tumor bearing host are tumor cell cytotoxic and the degree of cytotoxicity is equal to or greater than that from cells from the mononuclear fraction of blood or RLN's. The cytotoxicity was tumor specific and inhibited by serum from animals with tumors. Lastly, findings indicate that the synergistic decrease in tumor growth resulting from cyclophosphamide (CY) and C. parvum, was not the result of a greater decrease in serum inhibited by the 2 agents than by CY. Future investigations will aim at detecting a. whether the intra-tumor inoculation of NSSA's before primary tumor removal is more efficacious than systemic therapy for the management of micrometastases, (b) whether primary tumor irradiation with or without NSSA inoculation prior to removal will augment the suppressors of mcirometastases more than immediate removal of the tumor and subsequent therapy and (c) whether the presence or absence of a primary tumor influences effectiveness of treatment of metastases.